The general aim of this research is to examine whether enhanced activity of the sympathetic nervous system impairs the ability of individuals to perform fine motor skills. The proposed research represents a novel study that will investigate an unexplored functional connection between the autonomic nervous system and the motor system in humans. Manual dexterity is compromised in individuals with cardiac disease or with advanced age, who often have high levels of basal muscle sympathetic nerve activity (MSNA). This impaired manual dexterity may lead to a decrease in quality of life and capability for independent living. Independent research studies indicate that mental stress increases MSNA and force fluctuations during steady low-level contractions of hand muscles in humans. However, there are no studies that directly link enhanced MSNA with force fluctuations. Furthermore, there is evidence that suggests an increase in sensitivity of the la afferent circuit due to heightened SNA, and associations between the sensitivity of the la afferent circuit and force fluctuations in humans. Hence, we hypothesize that enhanced activity of the sympathetic nervous system impairs the ability of individuals to perform fine motor skills by altering the sensitivity of the la afferent circuit. The specific aims of this proposal are to determine whether increased MSNA increases force fluctuations (Aim 1), and to examine whether increased MSNA alters the sensitivity of the la afferent circuit (Aim 2) during low-force contractions of a hand muscle. To achieve these aims, MSNA, force fluctuations, single motor unit activity, stretch reflex, and H-reflex during steady contractions of a hand muscle will be measured when MSNA is experimentally manipulated by applying negative pressure to the lower body (LBNP). The findings of this study will constitute new information about the physiological mechanisms that impair manual dexterity in individuals with cardiovascular disease. The preliminary findings will form the foundation for an R01 application that will further identify the physiological mechanisms contributing to the impairment of fine motor skills in individuals who have or who are at risk of cardiovascular disease. The outcome of the study will lead to the development of interventions that can ameliorate the impaired manual dexterity in those individuals. [unreadable] [unreadable] [unreadable]